Catheter and guide tube for intracerebral application

ABSTRACT

A catheter for use in neurosurgery, and a method of positioning neurosurgical apparatus. The catheter has a fine tube arranged for insertion into the brain parenchyma of a patient with an external diameter of not more than 1.0 mm. The catheter and method may be used in stereotactically targeting treatment of abnormalities of brain function, and for the infusion of therapeutic agents directly into the brain parenchyma. This is advantageous when a therapeutic agent would have widespread unwanted effects which could be avoided by confining the delivery to the malfunctioning or damaged brain tissue.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a Continuation of application Ser. No.10/505,240, filed Feb. 22, 2005, which is a National Phase filing ofPCT/GB03/01030, filed Mar. 11, 2003, which claims the benefit ofpriority of Great Britain Patent Application No. 0205772.7, filed Mar.12, 2002. The disclosures of the prior applications are herebyincorporated by reference herein in their entirety.

TECHNICAL FIELD

The present invention relates to apparatus for use in neurosurgery, andto a method of positioning neurosurgical apparatus. The apparatus andmethod are particularly useful in stereotactically targeting treatmentof abnormalities of brain function, and for the infusion of therapeuticagents directly into the brain parenchyma. This would be particularlyuseful when a therapeutic agent given systemically will have widespreadunwanted side effects which would be avoided by confining the deliveryto the malfunctioning or damaged brain tissue.

BACKGROUND OF THE INVENTION

Examples of treating abnormalities of brain function include the acuteinfusion of Gamma-amino-butyric-acid agonists into an epileptic focus orpathway to block transmission, and the chronic delivery of opiates orother analgesics infused directly to the peri-aqueductal grey matter orto thalamic targets for the treatment of intractable pain. Also,cytotoxic agents can be delivered directly into a brain tumour.Intraparenchymal infusion could also be used to deliver therapeuticagents to brain targets that could not be delivered systemically becausethey will not cross the blood-brain barrier. For example, the treatmentof patients with Parkinson's disease, Alzheimer's disease, head injury,stroke and multiple sclerosis may be carried out by the infusion ofneurotrophic factors to protect and repair failing or damaged nervecells. Neurotrophins may also be infused to support neural graftstransplanted into damaged or malfunctioning areas of the brain in orderrestore function.

Intraparenchymal drug delivery has been demonstrated in non humanprimates and in rats. For intraparenchymal drug delivery to a human ornon-human brain, it is proposed that a catheter be implanted, and thedrug be pumped intermittently or continuously to the desired braintarget. For long term drug delivery, a pump containing a reservoir wouldbe implanted subcutaneously and the reservoir refilled as necessarypercutaneously through a palpable port.

In particular U.S. Pat. No. 6,042,579 discloses techniques for treatingneurodegenerative disorders by the infusion of nerve growth factors intothe brain.

In order to perform neurosurgery, the surgeon needs, in the firstinstance, to identify the position of the desired target. This isnormally achieved by fixing a stereotactic reference frame to thepatient's head which can be seen on diagnostic images, and from whichmeasurements can be made. The stereotactic frame then acts as a platformfrom which an instrument is guided to a desired target using astereoguide that is set to the measured coordinates. Once an instrumentis guided to the desired target, treatment can begin.

A number of difficulties are encountered in such neurosurgicalprocedures. Sub-optimal placement of the instrument being inserted maylead to significant morbidity or treatment failure. Brain targets fortreating functional disorders are usually deeply situated and have smallvolumes. For example, a desired target for treating Parkinson's diseaseis situated in the sub-thalamic nucleus and is 3-4 mm in diameter, or anovoid of 3-4 mm in diameter and 5-6 mm in length. Other targets such asthe globus palladus or targets in the thalamus are usually no more than1-2 mm larger. For such a small target sub-optimal placement of aslittle as 1 mm will not only reduce the effectiveness of the treatment,but may also induce unwanted side affects such as weakness, alteredsensation, worsened speech and double vision. However, functionalneurosurgical targets are often difficult or impossible to visualize ondiagnostic images, and so that actual position may be need to beinferred with the reference to visible landmarks in the brain and usinga standard atlas of the brain to assist the process. Anatomicalvariations between an individual and the atlas, and even betweendifferent sides of the same brain of an individual means that placementmay be sub-optimal. Other reasons for sub-optimal placement may resultfrom patient movement during image acquisition, or geometric distortionof imaging which can be intrinsic to the images method. Also, duringsurgery, brain shift can occur which might result from the change in thehead position from that during image acquisition to the position on theoperating table, from leakage of cerebrospinal fluid when a burr hole ismade with a subsequent sinking of the brain, and also from the passageof the instrument through the brain. Surgeons attempt to correct theseerrors by performing electrophysiological studies on the patientundergoing functional neurosurgery, kept awake during the procedures.

Intraparenchymal catheters may be guided to their targets in the brainusing stereotactic techniques. Typically, stereotactic localization of abrain target is accomplished by fixing the stereotactic base ring to theskull and identifying the position of the target using imagingtechniques. The position of the target is identified using threedimension co-ordinates by making measurements from radio-opaquefiducials attached to the stereotactic base ring. The stereotactic basering may then be used as a platform from which to guide instruments tothe target using a stereoguide on the stereotactic base ring that is setto the measured co-ordinates. The catheter may then be guided towardsthe target through the brain tissue after rigidifying it by theinsertion of a stiff wire through its bore. Alternatively, a straightwire may be guided to the target first, and the catheter introducedaround the wire so that one end (i.e. the inserted or distal end) islocated within the brain, and the opposite end (i.e. the external orproximal end) remains outside the brain. Once positioned, the externalend of the catheter can be fixed to the skull, and connected to a pumpwhereby the therapeutic agent may be administered. It will beappreciated that the outer diameter of the catheter tubing should be assmall as possible, particularly when especially sensitive parts of thebrain are to be treated, such as the mesencephalic targets, and aretherefore to be passed through by the catheter. Such highly sensitiveregions of the brain tend to be located in deep positions typicallybetween 70 and 100 mm from the surface of the skull, such as the brainstem. Of course, the thinner the catheter tubing, the greater thedeflection during insertion to those deep targets within the brain, andthe increased likelihood that placement will be sub-optimal.

SUMMARY OF THE INVENTION

The present invention seeks to optimize the placement of the catheterwhilst minimizing the trauma to the brain by utilizing small diametercatheter tubing.

According to a first aspect of the invention there is provided aneurosurgical catheter having a fine tube arranged for insertion intothe brain of a patient with an external diameter of not more than 1.0mm. It is preferred that the external diameter of the catheter is notmore than 0.7 mm, and even more preferred that it is not more than 0.65mm. Most preferably, its external diameter if not more than 0.5 mm. Thecatheter is preferably generally circular in cross section.

It is also preferred that the catheter is a deep target neurosurgicalcatheter and has a length of at least 40 mm, more preferably at least 70mm and most preferably at least 90 mm.

Since the fine tube is so fine, it is desirable for the catheter tofurther comprise a connector tube connected to one end of the fine tube,the connector tube being of greater diameter than the fine tube.Preferably the connector tube has an outer diameter of about 2 mm.Connection may be achieved by the inclusion of a hub disposed betweenthe fine tube and the connector tube. According to a preferredembodiment, the hub includes a passageway connecting the fine tube andthe connector tube, the passageway including a first passage in whichthe fine tube is securely inserted, a second passage in which theconnector tube is securely inserted and a further link passage disposedbetween the first and second passages.

In a preferred embodiment, the hub includes a cylindrical body and oneor more flanges by which the hub can be secured to the skull of thepatient. The hub may be secured using any fixing arrangement, includingglue and screws. It is particularly preferred that each flange includesan internal surface defining a countersunk hole by which the hub can besecured to the skull of a patient by screws.

Preferably, the hub includes a stop surface adjacent to where the finetube is secured to the hub. It is also preferred that the hub is taperedtowards that stop.

According to a second aspect of the invention, there is provided aneurosurgical instrument comprising a tube for insertion into the brainof a patient towards a desired target, the tube having a distal end forinsertion into the brain, a proximal end and a head disposed at theproximate end of the tube for attachment to the skull of the patient;and a catheter according to the present invention for insertion into thebrain of the patient via the tube. Other advantageous or preferredfeatures of the catheter are described above.

Preferably, the head of the guide tube includes an externally threadedsurface for engagement with the skull of the patient via an acryliccement. According to a preferred embodiment, the head includes a slotteddome structure, and the catheter has a hub having a stop at one endwhich abuts the dome structure once the fine tube has been inserted intothe guide tube. The slot is preferably shaped such that, as the catheteris bent over in the slot, it resists kinking. The domed structure ispreferably shaped such that, as the catheter is bent over in the slotwith the stop abutting the domed surface, the distal end of the catheterwill remain accurately located at its target. Reference is made toGB-A-2357700 which discloses a guide tube with a head having a domedstructure, the disclosure of which is incorporated herein by reference.

According to a third aspect of the invention there is provided aneurosurgical guide device comprising a tube for insertion into thebrain of a patient towards a desired target, the tube having distal endfor insertion, an opposite proximal end and a head disposed at theproximate end of the tube for attachment to the skull of the patient,characterized in that the internal diameter of the tube is not more than1 mm; wherein the tube is of a length such that the distal end fallsshort of the target by between 1 and 20 mm. Preferably the length issuch that the distal end falls short by between 5 and 10 mm.

According to a fourth aspect of the invention, there is provided amethod of positioning a catheter at a target in the brain of a patientcomprising; inserting a neurosurgical guide tube according to the thirdaspect of the present invention into the brain towards the target,wherein the distal end falls short of the target by between 5 and 20 mm;securing the head of the guide device to the skull; and inserting acatheter according to the present invention through the tube and to thetarget.

It is preferred that the catheter is positioned at a deeply positionedtarget of at least 40 mm from the surface of the skull, more preferablyat least 70 mm from the surface, and most preferably at least 90 mm fromthe surface of the skull.

The present application comprises a kit comprising:

one or more neurosurgical catheters according to the present invention;

one or more guide tubes for insertion into the brain of a patienttowards a desired target, each tube having distal and proximate ends anda head disposed at the proximate end of the tube for attachment to theskull of the patient; and

one or more guide wires.

Preferably, the kit according is provided in a pack having separatelymarked sections, wherein each section contains one catheter, one guidetube and one guide wire. This enables each set of elements (i.e. thecatheter, the guide tube and the guide wire) can be distinguished fromother sets of the elements. This is important when different sets ofelements are used on different sites of the brain.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present invention will be described by way of exampleonly with reference to the accompanying drawings in which:

FIG. 1 is a view of a catheter according to the present invention;

FIG. 2 is a view showing part of the catheter of FIG. 1 with internalfeatures shown in dotted lines;

FIG. 3 is an end view of the catheter from the right hand end of FIG. 2;

FIG. 4 shows a first phase of stereotactic insertion;

FIG. 5 shows a second phase of stereotactic insertion;

FIG. 6 shows a third phase of stereotactic insertion;

FIG. 7 shows a fourth phase of stereotactic insertion;

FIG. 8 is a perspective view of a guide tube with a dome-shaped head;

FIG. 9 is a sectional view of the guide tube of FIG. 8 with thedome-shaped head;

FIG. 10 is a schematic view showing the catheter of FIG. 1 insertedthrough a guide tube; and

FIG. 11 is a view of the catheter in situ once insertion is complete.

DETAILED DESCRIPTION OF THE INVENTION

As explained above, insertion of a catheter into particularly sensitiveregions of the brain leads to trauma on insertion which surgeons wish tominimize. The finer the catheter the less trauma the brain experiences.However, since the accuracy of insertion is crucially important, andsince these particularly sensitive areas of the brain are a considerabledistance from the skull surface, larger diameter catheters have beenconsidered to be necessary in order to accurately place the distal endof the catheter. However, the present invention allows much finercatheters to be used.

Example 1

FIGS. 1, 2 and 3 show a catheter 1 according to the present invention.The catheter 1 includes a length of fine tubing 2, the outer diameterwhich is no more than 1 mm, and most preferably no greater than 0.7 mm.It is even more preferred that the outer diameter be no more than 0.5mm. In this instance, the catheter tubing 2 is constructed frompolyurethane plastic and preferably from carbothane 55 DB20 (ThermedicsPolymer Products, Woburn Mass., USA). The fine tubing 2 is linked to alength of connector tubing 3 having an outer diameter of about 2 mm, viaa hub 4. The connector tubing 3 is, in this case, made from polyurethaneplastic, such as carbothane 85AB20, although other materials could alsobe used.

The hub 4 in this case is also constructed using polyurethane, such ascarbothane 72 DB20. Again, other materials may also be appropriate.

The fine tubing 2 is intended to be inserted into the brain of apatient, whereas the connector tubing 3 is intended to be connected tooutflow tubing of a pump by which a therapeutic agent may be pumpedintermittently or continuously to a desired brain target. For long termdrug delivery, the pump would be implanted subcutaneously and thereservoir refilled as necessary percutaneously through a palpable port.In this case, the connector tubing 3 would be connected to outflowtubing of the pump which would be tunneled subcutaneously from the pumpto the catheter. It's length will depend on particular installations andwill be cut to length appropriately.

The hub 4 includes a central body 5, which is generally cylindrical anda pair of diametrical opposing wings 6 each a containing a countersunkhole whereby the hub may be screwed to the outer surface of the skull ofthe patient.

The cylindrical body 5 of the hub 4 includes a passageway passingthrough its complete length. The passageway includes a first narrowpassage 8 of uniform diameter into which the fine tubing is inserted andsecurely held. The passageway also includes a second wide passage 9 ofuniform diameter into which the connector tubing 3 is inserted andsecurely held. Between the first and second passages 8, 9 is a thirdlinking passage 10 which is generally tapered in order to take accountof the different internal diameters of the fine tubing 2 and theconnector tubing 3. It will be noted that the ends of the third passage10 are of the same or very similar diameter to the internal diameters ofthe fine tubing 2 and the connector tubing 3.

From FIG. 2, it can be seen that the right hand end of the hub 4 isfrustoconical, and the end of the hub is planar and forms a stop 11, thesignificance of which will be understood from the description below.

Example 2

The insertion of the catheter will now be described. Firstly, astereotactic frame is attached to the patient's skull and the positionof the intracranial target is identified by imaging the patient wearingthe stereotactic frame and defining the position of the target as threedimensional co-ordinates. This step is explained in more detail in theintroduction to this patent specification and is a standard techniquewithin the field of neurosurgery.

Once the target has been defined, a stereoguide is used which is set tothe target coordinates. An appropriately sized guide tube having aninternal diameter of no more that 1 mm is directed into the brain in thedirection of the target. The guide tube is arranged with a head at oneend, which, once inserted, can be attached to the patient's skull, forexample by being bonded into a burrhole in the skull using an acryliccement.

Before insertion, the guide tube is cut to a length short of the target,and sufficiently short that, while it passes through brain tissue, itdoes not enter those parts of the brain which are particularly sensitiveto trauma. The distal end of the guide tube will typically fall severalmillimeters short of the target. The distance from the top of the headof the guide tube to the target is then measured, and a radio-opaquestylette is cut to length such that, when inserted down the guide tubeit's distal end reaches the planned target. This means that the stylettewill extend beyond the distal end of the guide tube.

The patient is then re-imaged in order to confirm the satisfactoryplacement of the stylette prior to removing the stylette and replacingit with the intraparenchymal catheter cut to the same length as thestylette. Again, the catheter will have an outer diameter of no morethan one millimeter although it will be appreciated that the catheter,the stylette and the guide tube will all be matched so that the catheterand stylette will fit properly within the guide tube. If it is desiredto use a very fine catheter of, say, 0.65 mm in outer diameter, anappropriate guide tube will also be used with an internal diameter of0.75 mm.

When the catheter is inserted, it is expected that it will be reinforcedduring insertion by the location of a stiff wire through it's bore, mostlikely made from tungsten. Once the catheter has been inserted in theguide tube, the stop 11 on the hub 4 will abut the head of the guidetube meaning that the distal end of the catheter has reached the target.The stiff wire is removed, and the fine tubing 2 is bent through about90° so that the hub 4 can be secured to the outer surface of the skullusing screws passing through the countersunk holes 7. To facilitate thebending, the head of the guide tube is dome shaped and arranged suchthat, during bending, not only will the fine tubing 2 not kink, but alsothe distal end of the fine tubing will not move. This will be explainedin more detail later in this specification.

The connector tubing 3 can then be connected to the outflow tubing of apump. Generally, the connector tubing 3, will be tunneled subcutaneouslyto the remotely positioned pump.

Example 3

In an alternative insertion technique, a number of phases or steps aretaken which are shown in FIGS. 4 to 7. As will be appreciated, smalldiameter catheters have a tendency to drift off the planned trajectoryduring insertion as a result of the flexibility inherent in a smalldiameter instrument. Since neurosurgical targets are often deeplysituated, typically 70-80 mm from the surface of the skull, andsometimes as much as 100 mm from the skull surface, the catheter mustnormally be very rigid, and therefore of a larger diameter.

Examples of possible targets include parts of the mesencephalonincluding the subthalamic nucleus, the substantia nigra and thepedunculor-pontine nucleus. This is a particularly critical region ofthe brain, where it is important to minimize trauma from the passage ofan instrument, which is typically situated about 70-80 mm from the skullsurface and contained within a volume which has a height ofapproximately 20-25 mm.

To facilitate insertion of very fine catheters into mesencephalictargets, insertion takes place as follows.

Firstly, a small diameter tungsten guide wire 22 of 0.6 mm in diameteris inserted in a tube 21 with an outer diameter of 1.7 mm and fixedwithin the tube 21 with a finger-tightened grub screw 23 such that thewire 22 protrudes from the distal end of the tube 21 by 25 mm. The tube21 is tapered towards its end for a length of 20 mm. The tube 21 andwire 22 can be seen in FIG. 4 showing the first phase of insertion inwhich the tube 21 with the wire 22 projecting from its end can be seen.The finger tightened grub screw 23 can be seen at the top of tube 21, inwhich the wire 22 is held. Insertion takes place from a stereotacticframe in which the target has been identified and defined in terms ofthree dimensional coordinates. The stereotactic frame carries astereoguide which has been modified in order to permit this technique.During the first phase of insertion shown in FIG. 4, the tube and wireare together lowered towards the target. In this case, the tube is 165mm in length, and since the tube 21 and the wire are inserted as a unit,the distance from the top of the tube to the tip of the guide wire 22 is190 mm. The wire 22 extends above the top of the tube by approximately150 mm. The stereoguide includes an upper clamp 24 and a lower clamp 25,and each of these clamps can be swiveled between a position ofengagement with the wire or tube which is being inserted or removed, anda position remote from that.

Once the guide wire 22 has reached its target, the upper clamp 24 isswiveled to clamp the proximal end of the guide wire 22. Once the grubscrew 23 has been loosened, the tube 21 can be withdrawn from the brainleaving the wire 22 in situ. Once the tube 21 has been raised up towardsthe upper clamp, the lower clamp can be swung across to clamp the nowexposed wire 22, and the upper clamp 24 can be released, as shown inFIG. 5. This allows the tube 21 to be removed altogether from the top ofthe wire 22.

A guide tube 31 is threaded onto the wire 22, and the upper clamp 24 isthen swung around and closed on the wire 22. The lower clamp 25 can thenbe released to allow the guide tube 31 to be inserted into the brain sothat its distance is approximately 1 or 2 cm short of the target, alsoshown in FIG. 7. The guide tube 32 has at its upper end a head with athreaded outer surface which permits the head to be screwed into thetapped burrhole in the patient's skull, thereby securing the guide tube31 securely in position. Further features of the head will become clearlater in this description.

Once the guide tube 31 is installed, the guidewire 22 may be removed andFIG. 7 shows that a 0.65 mm catheter 36 can then be inserted down theguide tube 31 to the target.

This method has the particular advantage that, on the first pass, theguide wire being stiffened by the tube 21 will hit the target, and thenby inserting a guide tube short of the target, the brain target will befixed and the guide tube will facilitate the insertion of a very fineinstrument to the target. For the treatment of certain conditions suchas Alzheimer's disease it is necessary to deliver nerve growth factorsto targets in the nucleus basalis through several in-dwelling catheters.If each catheter is only 0.65 mm in diameter, multiple fine catheterscan be inserted without substantially disrupting the tissue it isintended to regenerate.

In this insertion method, certain diameters of the wire 22, the insideof the tube 21, the outside of the tube 21 and the diameters of theguide tube 31 and the catheter 36 have been referred to. Of course, itwill be appreciated that different diameters may be suitable and thatthe important factor is that the outer diameter of the wire 22 and ofthe fine catheter 36 which passed through the mesencephalon are as fineas possible, and no larger than 1 mm in cross section. It is preferredthat the diameter is no more than 0.7 mm, and even more preferred thatit is not more than 0.65 mm.

The top part of the guide tube 31 is shown in FIGS. 8 and 9 from whichit will been seen that the top of the tube 41 carries a head 42 whichhas a threaded outer surface which can be screwed into the burrhole inthe skull through which instruments are inserted. The top of the tube 41opens into a slot 44 in the head 42. The head 42 is formed with a domestructure 45 in which the slot 44 is located.

As will been seen from FIG. 9, once the head has been secured into theskull, the catheter is located in the tube 41 and is then bent fromposition small y to position small z. The inner edge around which thecatheter is bent is radiused and is shaped in the slot 44 such that thecatheter will not kink and such that the distance from x to y is thesame as the distance from x to z so that the distal end of the catheteris not moved during the bending process.

It will be understood from FIGS. 8 and 9, that, in this embodiment, theguide tube 31 is formed with the head 42 including the threaded surface43 and the domed structure 45 as an integral unit.

Referring now to FIGS. 10 and 11, it will be seen that a catheter hasbeen inserted into the brain on a stiff wire (not shown) such that thestop 11 abuts the top of the dome structure 45. At this point, the stiffwire is removed and the distal end of the catheter is in the correctposition for treatment. The catheter is then bent over to the positionshown in FIG. 11 maintaining the stop 11 against the dome structure 45.FIG. 11 also shows how the hub 4 is attached via screws to the skull,and how the connector tubing 3 is directed off towards the pump.

It is preferred that the catheter delivers drugs through a single portat its distal end. This has advantages over catheters with multipleports at their distal end that may be used for intraparenchymal deliveryto the brain. In particular, the use of a single port minimizes the riskof the port becoming obstructed at the low flow rate anticipated forintraparenchymal delivery from the build up of proteinaceous material orgliotic ingrowth. A further advantage of having a single port at thedistal end of the intraparenchymal catheter is that it ensures drugdelivery at the defined target. The site of drug delivery from amultiport catheter is unpredictable, particularly at low flow rates.This is because flow will be maximal through the port with the lowestresistance. Even though the ports may be of an identical size, thedegree to which tissue obstructs any individual port will vary. The netresult will be off-axis drug delivery, probably from a single port,which will be sub-optimal for drug delivery to a small target.

Trauma to the brain is minimized upon insertion as a result of using avery fine catheter of no more that 1 mm in diameter and preferably lessthan 0.7 mm in diameter. In addition, the small diameter catheter makesit suitable for drug delivery to small targets in the brain stem such asthe substantia nigra and the pedunculopontine nucleus as well as toother small targets such as the nucleus basalis, the peri-aqueductalgrey matter and various thalamic nuclei.

During infusion of a therapeutic substance, the substance flowing fromthe catheter port or ports will preferably follow the path of leastresistance, i.e. flow back along the tissue/catheter interface, up tothe cortical surface and then into the CSF compartment.

Depending on the flow rate it will defuse variably into the tissues withan ovoid volume of distribution. Containing the drug within a smallbrain target can therefore be a problem. If, however, the catheter hasbeen inserted into the brain down an indwelling guide tube as in thepresent invention, then drug exiting the distal port flows back alongthe tissue/catheter interface until it reaches the guide tube. It thenflows preferably along the interface between the guide tube and thecatheter and out of the skull into the subgaleal compartment of thescalp. The volume of brain tissue exposed to the drug can therefore becontrolled by adjusting the length of the catheter that projects beyondthe guide tube as well as adjusting the flow rate. Such fine control isessential if one is to contain delivery of thugs such as neurotrophinswithin small brain targets.

Example 4

In a trial the intraparenchymal catheter of the present invention wasimplanted into the brains of five patients with advanced Parkinson'sdisease via a guide tube, the distal end of which was positioned justshort of the desired target. One patient had the catheter implantedunilaterally and four had bilateral implants into the dorsal putamen(i.e. the desired target). Recombinant-methionyl human glial cell linederived neurotrophic factor (r-met Hu GDNF) was chronically infusedthrough the catheters into their dorsal putamen via remotely positionedpumps (8626 Synchromed Pumps, Medtronic Inc, Minneapolis), implantedsubcutaneously in the abdominal wall. GDNF is a neurotrophic factor thathas been shown to reverse the symptoms of experimentally inducedParkinson's disease in animals. In this trial in humans it was infusedat flow rates ranging from 2 to 8 μl per hour and doses between 10.8 and43.2 micrograms/putamen/day. The patients were assessed preoperativelyand at six months using the internationally recognized and validatedscoring system for assessing the severity of Parkinson's disease, theUnified Parkinson's Disease Rating Score (UPDRS). At six months therewas a 40% improvement in the patients UPDRS scores. The infusions werewell tolerated and there were no major side affects.

1. A method for delivering a therapeutic agent to a desired target inthe brain of a subject, the method comprising the steps of: inserting aneurosurgical catheter comprising a fine tube with an external diameterof not more than 1.0 mm into the brain parenchyma of a patient; andintermittently pumping a therapeutic agent through the catheter to thedesired target.
 2. A method according to claim 1, wherein thetherapeutic agent comprises a neurotrophic factor.
 3. A method accordingto claim 2, wherein the neurotrophic factor is delivered to treat atleast one of Parkinson's disease, Alzheimer's disease and multiplesclerosis.
 4. A method according to claim 2, wherein the neurotrophicfactor is delivered to treat stroke or a brain injury.
 5. A methodaccording to claim 2, wherein the neurotrophic factor comprisesrecombinant-methionyl human glial cell line derived neurotrophic factor(r-met Hu GDNF).
 6. A method according to claim 1, wherein thetherapeutic agent comprises at least one of a Gamma-amino-butyric-acid,an opiate or an analgesic.
 7. A method according to claim 1, wherein thetherapeutic agent comprises a cytotoxic agent and the desired target inthe brain comprises a brain tumour.
 8. A method according to claim 1,further comprising a step of identifying the desired target fromdiagnostic images of the patient.
 9. A method according to claim 1,wherein the step of inserting a neurosurgical catheter comprises thesteps of forming a hole in the skull of the subject and stereotacticallyguiding the catheter to the desired target.
 10. A method according toclaim 1, wherein the desired target is located within at least one of amesencephalon, a subthalamic nucleus, a nucleus basalis, a substantianigra, a pedunculopontine nucleus, a brain stem, a peri-aqueductal greymatter and a thalamic nucleus.
 11. A method according to claim 1,further comprising a step of securing the catheter to the skull of thesubject after insertion.
 12. A method according to claim 1, wherein thestep of intermittently pumping a therapeutic agent through the catheterto the desired target in the brain comprises a step of chronicallyinfusing therapeutic agent to the desired target in the brain.
 13. Amethod according to claim 1, wherein the step of intermittently pumpinga therapeutic agent through the catheter to the desired target comprisesthe step of pumping therapeutic agent through the catheter at, duringperiods of infusion, a flow rate of between 2 and 8 micro-litres perhour.
 14. A method according to claim 1, further comprising a step ofimplanting a pump, a reservoir and tubing into the subject, wherein thepump, the reservoir and the tubing are used to intermittently pump thetherapeutic agent to the catheter.
 15. A method according to claim 1,wherein the step of intermittently pumping a therapeutic agent throughthe catheter to the desired target comprises the step of using aperistaltic pump.
 16. A method according to claim 1, wherein the finetube has an external diameter of not more than 0.7 mm.
 17. A methodaccording to claim 1, wherein the fine tube has an external diameter ofnot more than 0.65 mm.
 18. A method according to claim 1, wherein thefine tube has an external diameter of not more than 0.5 mm.
 19. A methodaccording to claim 1, wherein the fine tube is constructed frompolyurethane plastic.
 20. A method according to claim 1, wherein thestep of inserting a neurosurgical catheter comprises the step ofinserting the fine tube of the neurosurgical catheter into the brainparenchyma through a previously inserted guide tube.